eccD2 Family assigned · medium auto-curated

H37Rv Rv3887c · MTBC0 mtbc0_004121 · 509 aa · 4394401–4395930 (-) · RefSeq NP_218404.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ESX-2 secretion system protein EccD
MTBC0 PGAP re-annotationtype VII secretion system ESX-2 subunit EccD2
Revised (this work)Type VII secretion system ESX-2 subunit EccD2. Pfam: YukD (PF08817.17), EccD (PF19053.7).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt P9WNQ5 SwissProt · reviewed · Evidence at protein level
UniProt nameESX-2 secretion system protein eccD2

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred nameeccD2
eggNOG descriptionWXG100 protein secretion system (Wss), protein YukD
Orthologous group2B6TY
Gene Ontology (25) GO:0008150, GO:0009605, GO:0009607, GO:0020012, GO:0030682, GO:0042783, GO:0043207, GO:0044403, GO:0044413, GO:0044415, GO:0044419, GO:0050896 +13 more

Orthology-based transfer (eggNOG 5.0.2, diamond). EC/KO/GO/CAZy are computed annotations, not manual curation; cross-check against the primary literature before treating a specific reaction as established.

Conservation & selection (intra-MTBC, 145 209 strains)

pN/pS 1.059 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 6 synonymous, 17 missense, 0 nonsense, 6 frameshift
Disruption 6 distinct premature-stop/frameshift site(s); most common in 0.63% of strains (922) · convergent

pN/pS from segregating SNPs (singletons removed) normalised by possible sites. Low pN/pS = purifying selection (a strong signal that a "hypothetical" is a real, constrained gene). A high pN/pS is ambiguous: relaxed constraint or positive selection (drug resistance, antigenic variation) inflate it; e.g. rpoB/katG/pncA score high here for resistance, not loss of function. A clonal disruption (one allele over a clade) suggests lineage pseudogenisation; a convergent one (many independent alleles) is typical of resistance loss-of-function.

Domains (Pfam, hmmscan --cut_ga)

PfamAccessioni-EvalueResiduesDescription
YukDPF08817.17 1.2e-1213–93 WXG100 protein secretion system (Wss), protein YukD
EccDPF19053.7 6.6e-28141–509 EccD-like transmembrane domain

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: mycP2 (membrane-anchored mycosin), high confidence from genomic context alone (score 952 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3886c mycP2 membrane-anchored mycosin 952 952 ctx neighborhood:881 cooccurence:531
Rv3888c membrane protein 993 949 ctx neighborhood:881 cooccurence:568 textmining:870
Rv3884c eccA2 ESX-2 secretion system protein EccA 916 899 ctx neighborhood:794 cooccurence:519
Rv3885c eccE2 ESX-2 secretion system protein EccE 884 885 ctx neighborhood:881
Rv3899c hyp hypothetical protein 879 880 ctx cooccurence:772 coexpression:430
Rv3894c eccC2 ESX-2 type VII secretion system protein EccC 880 876 ctx cooccurence:762
Rv3895c eccB2 ESX-2 secretion system protein EccB 851 828 ctx cooccurence:764
Rv1782 eccB5 ESX-5 type VII secretion system protein EccB5 824 788 ctx cooccurence:734
Rv1783 eccC5 ESX-5 type VII secretion system protein EccC5 877 781 ctx cooccurence:637 textmining:462
Rv2423 hyp hypothetical protein 747 747 ctx cooccurence:747
Rv0256c PPE2 PPE family protein PPE2 712 713 ctx cooccurence:711
Rv2067c hyp hypothetical protein 708 709 ctx cooccurence:707
Rv1796 mycP5 membrane-anchored mycosin MycP 698 697 ctx cooccurence:676
Rv2082 hyp hypothetical protein 678 679 ctx cooccurence:441 coexpression:446
Rv3446c hyp hypothetical protein 672 672 ctx cooccurence:661

STRING combines evidence channels (neighborhood, fusion, cooccurrence, coexpression, experimental, database, text-mining) into a 0–1000 score. The ctx badge marks edges carried by the genomic-context channels (conserved neighborhood, fusion, phylogenetic co-occurrence), which are independent of orthology and structure and the strongest signal for an unknown gene. The no text-mining column recomputes the score from data alone, so a link that does not depend on the literature is visible. Association is a function hypothesis, not proof: corroborate with the operon context and the primary literature before assigning a function.

Evidence

  • Legacy H37Rv annotation: ESX-2 secretion system protein EccD
  • MTBC0 PGAP product: type VII secretion system ESX-2 subunit EccD2
  • Pfam (hmmscan --cut_ga): YukD PF08817.17 (E=1e-12), EccD PF19053.7 (E=7e-28)
  • (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)

Sources

  • Ancestral sequence & coordinates: Harrison LB et al. (2024), An imputed ancestral reference genome for the MTBC, doi:10.1101/2023.09.07.556366
  • Product annotation: NCBI PGAP on MTBC0; legacy from H37Rv NC_000962.3 (RefSeq NP_218404.1)
  • Domains: Pfam-A via hmmscan --cut_ga — YukD (PF08817.17), EccD (PF19053.7)
  • Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
  • Controlled vocabulary: eggNOG-mapper 2.1.12 (Cantalapiedra et al. 2021, doi:10.1093/molbev/msab293), eggNOG 5.0 DB (Huerta-Cepas et al. 2019) — OG 2B6TY
  • Curated reference: UniProt P9WNQ5 (SwissProt, reviewed; Evidence at protein level)
  • Intra-MTBC selection: pN/pS and disruption from SPDI variants of 145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 61 functional partner(s); context anchor mycP2
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_004121|Rv3887c|eccD2
MTAPHKVAFPARCAVNICYDKHLCSQVFPAGIPVEGFFEGMVELFDADLKRKGFDGVALPAGSYELHKINGVRLDINKSLDELGVQDGDTLVLVPRVAGESFEPQYESLSTGLAAMGKWLGRDGGDRMFAPVTSLTAAHTAMAIIAMAVGVVLALTLRTRTITDSPVPAAMAGGIGVLLVIGALVVWWGWRERRDLFSGFGWLAVVLLAVAAACAPPGALGAAHALIGLVVVVLGAITIGVATRKRWQTAVVTAVVTVCGILAAVAAVRMFRPVSMQVLAICVLVGLLVLIRMTPTVALWVARVRPPHFGSITGRDLFARRAGMPVDTVAPVSEADADDEDNELTDITARGTAIAASARLVNAVQVGMCVGVSLVLPAAVWGVLTPRQPWAWLALLVAGLTVGLFITQGRGFAAKYQAVALVCGASAAVCAGVLKYALDTPKGVQTGLLWPAIFVAAFAALGLAVALVVPATRFRPIIRLTVEWLEVLAMIALLPAAAALGGLFAWLRH